A study to elucidate the thermodynamic situation of transfer ribonucleic acids (tRNA) in aqueous solution is proposed. The study will provide thermodynamic data related to the interaction between nucleic acids and the aqueous environment and to the structure and stability of tRNA in solution. Such information should prove useful in developing a more detailed picture of protein synthesis, particularly those aspects which involve tRNA. The proposed project will focus on two aspects of the general problem. The first is the study of the thermodynamic situation of model compounds in aqueous solution. Data will be obtained by calorimetric measurements of the heat of solution and heats of dilution of nucleic acids and analogous model compounds in various solvents. Such information is necessary to develop a quantitative understanding of the role which the aqueous environment plays in the structure and stability of tRNA. The second aspect will include studies of the thermal unfolding of specific tRNAs as a function of temperature, Mg ions, and salt concentration. Relevant data will be obtained from equilibrium spectrophotometric studies and from microcalorimetric experiments. Interpretation of such data will be based on a thermodynamic model recently proposed. The purpose of such studies will be to test the general validity of the model. If the general validity of this model is established, extension of thermodynamics studies of tRNA to such areas as condon-anticondon recognition and nucleic acid - synthetase interaction will be possible.